1. Field of the Invention
The application relates to a process for preparing 3,6-dihydro-2H-pyran-2-carboxylic esters via a thermal hetero Diels-Alder reaction from 1,3-dienes and esters of glyoxylic acid.
2. Brief Description of the Prior Art
The hetero Diels-Alder reaction of conjugated dienes with carbonyl compounds is one of the fundamental reactions in organic chemistry. Conjugated dienes can in principle be reacted thermally with glyoxylic esters in a hetero Diels-Alder reaction to give 3,6-dihydro-2H-pyran-2-carboxylic esters.
J. Org. Chem. USSR, 1970, 6, 411 discloses the reaction of 2,3-dimethyl-1,3-butadiene or isoprene with ethyl glyoxylate in a thermal hetero Diels-Alder reaction to give the corresponding 3,6-dihydro-2H-pyran-2-carboxylic esters. To this end, diene, ethyl glyoxylate and hydroquinone are mixed on the 500 mmol scale and then heated to 130° C. The 3,6-dihydro-2H-pyran-2-carboxylic esters are obtained on this laboratory scale in yields of 40 to 74%.
According to Tetrahedron 1993, 49, 4639-4650, 10 mmol of ({[(3E)-2-(benzyloxy)-3,5-hexadienyl]oxy}methyl)benzene and other dienes are mixed with butyl glyoxylate and hydroquinone and heated to 130° C. for 18 hours. After workup, cycloadducts are obtained in 60% yield.
Org. Magn. Res. 1983, 21, 94-107 also discloses the preparation of butyl 3,6-dihydro-2H-pyran-2-carboxylates via a thermal Diels-Alder reaction from 1,3-butadiene and butyl glyoxylate on a small scale.
More highly substituted, conjugated dienes generally react at relatively low temperatures and in better yields. For example, reactivity and yield increase in the order 1,3-butadiene<2-methyl-1,3-butadiene<2,3-dimethyl-1,3-butadiene.
In recent times, progress has been made on the route of catalyzed hetero Diels-Alder reactions with glyoxylic esters. The advantage of these methods described, for example, in Tetrahedron Lett. 1998, 39, 1161-1164, J. Chem. Soc., Chem. Commun. 1996, 2373-2374, J. Chem. Soc., Perkin Trans, 1, 1997, 2345-2349 and J. Org. Chem. 1995, 60, 5757-5762 is frequently a relatively low reaction temperature. A disadvantage of the catalyzed syntheses is that expensive (BiCl3, Me—Al[(S)-BINOL], Zn(OTf)2, and toxic (SnCl2, Cu compounds) catalysts which are often difficult to prepare are used which make the process uneconomical. In addition, the removal of the product is distinctly more complicated. For most of these examples, industrial scale reaction is impossible for environmental reasons, since heavy metal wastes (Bi, Sn, Cu) occur.
J. Org. Chem. 1995, 60, 5757-5762 describes the reaction of glyoxylic esters with conjugated dienes catalyzed by a copper(II)-bisoxazoline complex. In this reaction, isopropyl glyoxylate, for example on the 10 mmol scale, is reacted with 5 to 10 equivalents of 1,3-butadiene in dichloro-methane in the presence of a catalyst which is formed in situ from Cu(OTf)2 and a chiral oxazolidinone within 5 days to give the corresponding 3,6-dihydro-2H-pyran-2-carboxylic ester. The yield obtained is 55%.
All of the above-mentioned publications on thermally catalyzed reaction of conjugated dienes with glyoxylic esters to give 3,6-dihydro-2H-pyran-2-carboxylic esters have the common disadvantage that the reaction comprises a procedure which (for the purposes of the present application) is referred to as a batch process. In this batch process, all reaction components, i.e. the diene and the glyoxylate (and also the customarily used stabilizer), are initially combined directly at low temperature and mixed with one another and then brought to the required reaction temperature of generally more than 100° C. by heating. These batch processes are only described for performance on the laboratory scale.
However, this procedure, in particular in a reaction on a relatively large scale, is highly questionable for safety reasons, since conjugated dienes, especially 1,3-butadiene, tend to thermally polymerize at elevated temperature and the associated adiabatic temperature increase can lead to thermal decomposition through to explosion of the reaction mixtures.
The strongly exothermic polymerization of 1,3-butadiene sets in, for example, at temperatures above 100° C. with a heat of reaction of about 1350 kJ/kg. Immediately after the polymerization, strongly exothermic decomposition of the polymer occurs from about 295° C. Heat liberated by the decomposition is about 1500 kJ/kg (Odian “Principles of Polymerization” p. 264-Table 3-14. )
These factors lead to a rise in the rate of reaction and an exponential rise in the heat output. The consequence is an exothermic reaction which can no longer be controlled (known as a runaway reaction). This is a barrier in particular to conversion of these reactions to the industrial scale and therefore to an economical utilization of this synthetic route existing in principle.
It is therefore an object of the present invention to provide a process for preparing 3,6-dihydro-2H-pyran-2-carboxylic esters via a thermal hetero Diels-Alder reaction from 1,3-dienes which has no inherent safety problem unlike the existing batch processes and therefore facilitates a synthesis on relatively large scales while at the same time obtaining good yields of the desired product.